Citations

Abstract IER3 (formerly IEX-1) encodes a 27-kDa glycoprotein that regulates death receptor–induced apoptosis, interacts with NF-κB pathways, and increases expression rapidly in response to cellular stresses such as irradiation. Animal models, gene expression microarray experiments, and functional studies in cell lines have suggested a potential role for IER3 in oncogenesis, but, to date, no abnormalities of IER3 at the DNA level have been reported in patients with neoplasia. Here, we describe breakpoint cloning of a t(6;9)(p21;q34) translocation from a patient with a myelodysplastic syndrome (MDS), facilitated by conversion technology and array-based comparative genomic hybridization, which revealed a rearrangement translocating the IER3 coding region away from critical flanking/regulatory elements and to a transcript-poor chromosomal region, markedly decreasing expression. Using split-signal and locus-specific fluorescence in situ hybridization (FISH) probes, we analyzed 204 patients with diverse hematological malignancies accompanied by clonal chromosome 6p21 abnormalities, and found 8 additional patients with MDS with IER3 rearrangements (translocations or amplification). Although FISH studies on 157 additional samples from patients with MDS and a normal-karyotype were unrevealing, and sequencing the IER3 coding and proximal promoter regions of 74 MDS patients disclosed no point mutations, reverse transcription-PCR results suggested that dysregulated expression of IER3 is common in MDS (61% >4-fold increase or decrease in expression with decreased expression primarily in early MDS and increased expression primarily in later MDS progressing toward leukemia), consistent with findings in previous microarray experiments. These data support involvement of IER3 in the pathobiology of MDS. [Cancer Res 2009;69(19):7518–23]

Large dural arteriovenous malformations (DAVMs) accompanied by cardiac failure usually carry a poor prognosis with a high risk of morbidity and death. The authors report on the case of a male neonate with a massive DAVM who presented at birth with macrocephaly and high-output cardiac failure. The child initially underwent treatment with surgical clipping of the large main feeding artery. Hydrocephalus, thought to be due to venous hypertension, developed when the boy was 8 months old. The condition resolved after interventional embolization treatment. The patient did not require placement of a ventriculoperitoneal shunt. At 21 months of age, the child had near normal development without any focal neurological deficits.

Purpose The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC). Patients and Methods Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided α level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC. Results A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups. Conclusion For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.

Hydrogen sulfide (H 2 S) has long been associated with the gastrointestinal tract, especially the bacteria-derived H 2 S present in flatus. Along with evidence from other organ systems, the finding that gastrointestinal tissues are capable of endogenous production of H 2 S has led to the hypothesis that H 2 S is an endogenous gaseous signaling molecule. In this review, the criteria of gasotransmitters are reexamined, and evidence from the literature regarding H 2 S as a gaseous signaling molecule is discussed. H 2 S is produced enzymatically by gastrointestinal tissues, but evidence is lacking on whether H 2 S production is regulated. H 2 S causes well-defined physiologic effects in gastrointestinal tissues, but evidence for a receptor for H 2 S is lacking. H 2 S is inactivated through enzymatic oxidation, but evidence is lacking on whether manipulating H 2 S oxidation alters endogenous cell signaling. Remaining questions regarding the role of H 2 S as a gaseous signaling molecule in the gastrointestinal tract suggest that H 2 S currently remains a molecule in search of a physiologic function. Antioxid. Redox Signal. 12, 1135–1146.